PT - JOURNAL ARTICLE AU - Faekah Gohar AU - Janneke Anink AU - Halima Moncrieffe AU - Lisette W.A. Van Suijlekom-Smit AU - Femke H.M. Prince AU - Marion A.J. van Rossum AU - Koert M. Dolman AU - Esther P.A.H. Hoppenreijs AU - Rebecca ten Cate AU - Simona Ursu AU - Lucy R. Wedderburn AU - Gerd Horneff AU - Michael Frosch AU - Dirk Foell AU - Dirk Holzinger TI - S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis AID - 10.3899/jrheum.170438 DP - 2018 Jan 15 TA - The Journal of Rheumatology PG - jrheum.170438 4099 - http://www.jrheum.org/content/early/2018/01/05/jrheum.170438.short 4100 - http://www.jrheum.org/content/early/2018/01/05/jrheum.170438.full AB - Objective Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response. Methods S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded. Results Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133–440 ng/ml] and MTX (median 220, IQR 100–440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125–615) ng/ml versus 150 (IQR 87–233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150–624) ng/ml versus 151 (IQR 83–201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10. Conclusion Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.